The Practice Nurse was getting a bit bored, sitting in the travel clinic listening to all of these people wanting advice for their various holiday destinations. There was only so much advice she could give for beach holidays to Ibiza and Magaluf. So when she opened the next patient record and saw it was a couple about to go on a wildlife spotting trip to Madagascar, she said out loud… “ooh that’s a bit more like it!” and called them in…

​“We have been reading on the internet” they stated, “and we are worried about plague”

The Practice Nurse raised an eyebrow and gazed at them for a moment to see if they were joking, while her mind flicked between the sound track of the Dreamworks Madagascar movie and her school days hearing about the Black Death, plagues ripping across Europe, and the ring-a-ring-a-roses nursery rhyme…

PlagueHistory is full of stories of the plague, and I too can remember listening to teachers at school telling tales of how this horrendous disease swept across Europe killing everyone who came into contact with it. But is this really true?

In fact there have only been three main pandemics of plague in the past 200 years, however they did have major mortality rates, hence the common name the “Black Death”!

The first was the Plague of Justinian (541-542), which affected the Eastern Roman Empire, especially Constantinople and the Mediterranean region. It is estimated to have killed 25-50 million people during the initial pandemic and in the 200 years after when it continued to circulate. This was up to a quarter of the World’s population at this time! Justinian I was Emperor of Rome when the pandemic started; apparently he caught the plague but survived.

The next pandemic was the Black Death (1347-1353) which killed an estimated 30-60% of the population of Europe, about 100-125 million people. The result was a number of social, religious and political upheavals that shaped the future of Europe including movement of people in to cities, decline of the power of the Church and increased power of Governments.

The last big pandemic was the Third Pandemic which began in 1855 and continued officially until 1959 although some argue that current cases are all part of the tail end of the Third Pandemic. The Third Pandemic killed over 10 million people but by this time scientists had worked out that rat fleas were the route by which plague was being spread and therefore control of rat populations helped to stop plague causing as much devastation as it had during the Black Death.

All of these pandemics are thought to have arisen in China and spread via trade routes across Asia and Europe. During these earlier pandemics black rats and their fleas where the main cause of plague but in recent times there has been a shift from black rats to other types of rats as well as small mammals such as ground squirrels, rabbits and hares and even cats and dogs…

…The Practise Nurse’s attention returned to the room and she saw the couple were actually genuinely concerned!!

“Plague? Yes, umm tell me …why are you worried about plague?” she asked as she quickly recovered her train of thought.

“There’s plague in Madagascar and we don’t want to get it of course” they replied quite bluntly.

“Okay, let me see what I can find out …where are you going exactly …as these things often occur in isolated or specific areas?” the Practice Nurse replied calmly whilst opening the NathNac and the WHO websites to see what the state of play was with plague around the world and in particular Madagascar.

What is plague?Plague is an infectious disease caused by the bacterium Yersinia pestis, named after Alexandre Yersin, a Swiss/French physician and bacteriologist, who discovered the bacterium in 1894 during an epidemic of the plague in Hong Kong. Y. pestis is a small pleomorphic Gram-negative bacillus in the family of enterobacteriaceae like E. coli and Klebsiella spp..

Plague is spread through a cycle that traditionally involved rats being bitten by infected fleas. These infected rats were then bitten by other fleas which then became infected from the rats. The bacterium multiplied in the gut of the flea causing obstruction and when the flea next bit it regurgitated these bacteria into the new host. The infectious dose of Y pestis can be as little as 100 bacteria.

So where do you find plague in modern times?Most cases of plague today are reported from Madagascar and Sub-Saharan Africa (particularly Democratic Republic of Congo, Tanzania and Uganda) but there are still cases acquired in Asia, the Soviet Union, South America and even the USA. Most cases occur in rural areas where there is contact with animals that are the source of infected fleas.

Click for larger image

​How high risk is Madagascar?Plague is endemic on the Plateaux of Madagascar, including Ankazobe District, where the current outbreak originated. A seasonal upsurge, predominantly of bubonic plague, usually occurs yearly between September and April. In 2017 the seasonal upsurge began early in August and was predominantly pneumonic plague. During the epidemic, spread occurred from rural to urban areas, including the capital Antananarivo and port cities. This means that the plague has the potential to escape Madagascar and affect countries that have air or sea links such as Ethiopia, Kenya, Tanzania, Mozambique, South Africa, Seychelles, Comoros, Reunion, and Mauritius.

The concern is that from these “direct contact” countries plague has the potential to spread around the world. Therefore the Government of Madagascar and the World Health Organisation responded quickly with enhanced surveillance, diagnosis, infection control, antibiotic treatment and prophylaxis amongst other measures and the outbreak was declared over on the 27th November 2017. In total there were over 2400 cases and 209 deaths; a mortality of 9%.

Plague in Madagascar

​How does plague present?The incubation period of plague is 1-7 days. Plague usually begins with a non-specific flu-like illness: fever, chills, muscle pains, nausea, sore throat and headaches. Plague then usually manifests one of three clinical patterns:

Bubonic – lymphadenitis occurs in the lymph nodes that drain the site where the infected flea bite occurred. These large inflamed and suppurating lymph nodes are called buboes, hence the name bubonic plague.

Septicaemic – blood stream infection can occur following bubonic plague (secondary septicaemic plague) or with the development of buboes (primary septicaemic plague). Shock and disseminated intravascular coagulation are common.

Pneumonic – infection of the lungs, in the form of severe pneumonia, can be primary from infected droplet transmission or secondary from haematogenous seeding. Pneumonic plague can spread person-to-person via droplets.

Untreated bubonic plague has a mortality of 50-60% whereas untreated septicaemic and pneumonic plague are almost invariably fatal.

Plague is a notifiable disease in all countries. In the UK a case would be notified to Public Health England who would then alert the WHO.

How do you diagnose plague?Plague is tricky to diagnose because we wouldn’t usually think about it as a diagnosis in the UK until it is too late. Y. pestis does grow in the laboratory but it takes time. On blood agar at 24 hours there will be small non-descript grey-white colonies that look similar to other enterobacteriaceae, only smaller. It is a non-lactose fermenter and is indole and urease negative. Most laboratory identification systems will identify it including API and MaldiTOF. It is a Category 3 organism and samples should be processed in a Biological Safety Level 3 facility such as that used for processing respiratory samples.

The main sample types are pus from buboes, blood cultures and sputum BUTY. pestis is potentially infectious to the person taking the samples and so these should only be taken by those experienced in taking such samples. Remember to identify the sample as “high risk” for laboratory staff too.

Serology can be done if treatment is started before samples are taken and a four-fold rise in specific antibody is diagnostic. PCR can also be performed on pus, tissue and CSF to identify the bacterium.

There is a rapid antigen detection test approved by the WHO for the use in outbreaks which has been used with great success in Madagascar and Sub-Saharan Africa. It is a bit like a pregnancy test and detects an antigen expressed by the bacterial cell. If the test is positive then it is highly predictive of plague but a negative doesn’t rule out the diagnosis.

How is plague treated?The earlier treatment is started the better the outcome. Antibiotics should be started immediately plague is considered and at least within the first 2 days of illness otherwise the mortality is very high.

The good thing about Y. pestis is that it is sensitive to lots of different antibiotics. The main treatments are:

​Duration of treatment: 7-14 days (10-14 days if using tetracyclines or Doxycycline as these are bacteriostatic)

Travel to MadagascarThe risk of travellers acquiring plague in Madagascar is low. Travellers should be encouraged to wear closed shoes, long trousers and long sleeves to limit insect bites, use insect repellents such as DEET to prevent fleas biting, sleep under mosquito nets and stay away from dead animals. It’s all pretty common sense advice to limit exposure to potentially infected fleas.

So the couple in the travel clinic were reassured that the current outbreak of plague on Madagascar was over. They were told that plague was endemic on the island and so the risk was never going to be zero. They were given sensible advice about avoiding flea bites as well as mosquito bites because they are at higher risk in Madagascar of catching malaria. Their vaccinations were checked and updated and they were given the appropriate length of antimalarial prophylaxis with Doxycycline.

Having seen that Doxycycline was a potential treatment of plague the Practice Nurse wondered if the Doxycycline would prevent plague?… but decided that would be a conversation to be had with a Microbiologist and they probably wouldn’t appreciate her “speculative interest” in plague prophylaxis and treatment so it wasn’t a conversation she was going to have…. and for the record there is no recommended prophylactic plague strategy!

P.S. This is Bug Blog 200! Hooray for us… and for all of you for reading them!